>> What does Myriad say works, apart from their fancy "profen"?..... <<
Here's the entire spiel, from their website........
myriad.com
Alzheimer's Disease and Current Research
Alzheimer's disease is a degenerative neurological condition affecting nearly half of those over 85, with an estimated 4 million cases in the United States alone. The disease is the leading cause of dementia. Current approved treatments, such as cholinesterase inhibitors, temporarily relieve symptoms without meaningfully impacting progression of the underlying disease. Alzheimer's disease is marked by progressive cognitive decline and by the accumulation of amyloid plaques and neurofibrillary tangles in the brain. The major structural component of these plaques is amyloid beta peptide, specifically amyloid beta-42 (Abeta42). Many researchers now believe that Abeta42 plays an essential role in initiating the neurodegeneration leading to the onset of Alzheimer's disease. Current research is focused on compounds that decrease levels of Abeta42 with the hope of preventing or slowing the progression of Alzheimer's disease.
MPC-7869 for the Treatment and Prevention of Alzheimer's Disease
MPC-7869 holds promise as a safe and effective drug for the treatment and prevention of Alzheimer's disease. MPC-7869 is the pure R-enantiomer form of flurbiprofen - an NSAID (non-steroidal anti-inflammatory drug) with 25 years of clinical experience behind it. Unlike NSAIDs, however, MPC-7869 is not an inhibitor of cyclooxygenase enzymes (COX-1 and COX-2). The compound modulates the signal transduction and transcription activation pathways associated with nuclear factor kappa B (NFkB), a principle transcription factor in the expression of many molecules involved in cell growth, cell death and inflammation. In addition, MPC-7869 has recently been shown to reduce Abeta42 peptide levels in vitro and in vivo, and reduce amyloid pathology in the brain. MPC-7869 has an excellent safety profile and is very potent in animal models of cancer and Alzheimer's disease.
The Effect of MPC-7869 on Abeta40 and Abeta42
Production in Cultured Human Neuroglioma Cells
Preclinical Studies
MPC-7869 has the potential to be the first drug to have a significant impact on the precise molecular causative agent of Alzheimer's disease and, thereby, slow or halt disease progression.
A large number of epidemiological studies have indicated that chronic use of NSAIDs reduces the risk of developing Alzheimer's disease.1 Most recently, the 'Rotterdam study', a long-term prospective study, which followed almost 7,000 patients for nearly seven years, found that the use of traditional NSAIDs for two years or more provided 80 percent protection against the development of Alzheimer's Disease.2 Moreover, the NSAID indomethacin appeared to slow the cognitive decline in patients with moderate Alzheimer's Disease in a placebo-controlled pilot study, although GI toxicity (accounting for over 20% dropout of the indomethacin treatment group) limited the scale of the study.3 Significantly, as described below, indomethacin has anti-amyloid activities in addition to its activity as an NSAID.
Recent preclinical data suggests that a certain subset of marketed NSAIDs selectively lowers the levels of the Abeta42 peptide, the molecule widely accepted to initiate the pathological cascade of events that leads to nerodegeneration in the Alzheimer's brain.4 In this study, indomethacin, ibuprofen and sulindac sulphide selectively decreased the Abeta42 peptide produced from a variety of cultured cells by up to 80%. The Abeta42-lowering activity of these NSAIDs was independent of cyclooxygenase (COX) inhibition and was not exhibited by most marketed NSAIDs; aspirin, naproxen, meloxicam, sulindac sulfone, SC-560 and celecoxib showed no ability to lower Abeta42 production.
Significantly, short-term administration of ibuprofen to a transgenic mouse model of Alzheimer’s disease lowered brain levels of Abeta42 in these mice.4 Independent studies of chronic high-dose ibuprofen administered to transgenic mice resulted in a significant reduction in amyloid plaque pathology in the brain and prevented the decline in behavioral measures of cognitive function.5, 6 In addition, it was recently reported that this regimen is capable of reversing memory loss and restoring normal memory in transgenic mice.7
MPC-7869 shows promise as a safe, effective drug for the treatment and prevention of Alzheimer's disease.
In support of these preclinical findings, a re-analysis of the Rotterdam results demonstrated that the protection against Alzheimer’s disease progression conferred by NSAID use was entirely attributable to that subset of NSAIDs (indomethacin, ibuprofen, and sulindac sulfide) that specifically lowers Abeta42.8 Recent clinical trials with rofecoxib and naproxen have yielded results consistent with the above observations. Neither naproxen (nonselective COX inhibitor) nor rofecoxib (COX-2 selective) exhibit Abeta42-lowering activity and neither drug demonstrated a slowing of the progression of Alzheimer’s disease.9
Unfortunately, the high doses of ibuprofen and the other NSAIDs used in the preclinical studies entail an unacceptably high risk of GI toxicity. A number of companies have been evaluating gamma-secretase inhibitors as potential therapeutics for Alzheimer's Disease. However, these have recently been shown to be toxic, probably due to the inhibition of other essential gamma-secretase functions.10
Myriad, in collaboration with external researchers, has completed preclinical studies indicating that MPC-7869 is a potent and selective Abeta42-lowering agent in vitro and in vivo. The concentrations of MPC-7869 required to see a significant Abeta42-lowering effect are readily achievable in humans at doses that have been well-tolerated.
Current Clinical Trial Information
Alzheimer's Disease Clinical Trial
References
1
McGeer PL, Schulzer M, McGeer EG. Arthritis and anti-inflammatory agents as possible protective factors for Alzheimer's disease: a review of 17 epidemiologic studies. Neurology. 1996 Aug;47(2):425-32.
Article | PubMed
2
in t' Veld BA, Ruitenberg A, Hofman A, et al. Nonsteroidal antiinflammatory drugs and the risk of Alzheimer's disease. N Engl J Med. 2001 Nov 22;345(21):1515-21.
PubMed
3
Rogers J, Kirby LC, Hempelman SR, et al. Clinical trial of indomethacin in Alzheimer's disease. Neurology. 1993 Aug;43(8):1609-11.
PubMed
4
Weggen S, Eriksen JL, Das P, et al. A subset of NSAIDs lower amyloidogenic Abeta42 independently of cyclooxygenase activity. Nature. 2001 Nov 8;414(6860):212-6.
PubMed
5
Lim GP, Yang F, Chu T, et al. Ibuprofen suppresses plaque pathology and inflammation in a mouse model for Alzheimer's disease. J Neurosci. 2000 Aug 1;20(15):5709-14.
PubMed
6
Lim GP, Yang F, Chu T, et al. Ibuprofen effects on Alzheimer pathology and open field activity in APPsw transgenic mice. Neurobiol Aging. 2001 Nov-Dec;22(6):983-9.
PubMed
7
Westerman M, et al. Ibuprofen reverses memory loss in transgenic mice modeling Alzheimer's disease. The 8th International Conference on Alzheimer's Disease and Related Disorders. 2002.
8
Breteler M, et al. Abeta-42 Peptide Lowering NSAIDs and Alzheimer's Disease. The 8th International Conference on Alzheimer's Disease and Related Disorders. 2002. Abstract number: 1071.
9
Aisen P, Block G, et al. Results of a multicenter trial of rofecoxib and naproxen in Alzheimer's disease. The 8th International Conference on Alzheimer's Disease and Related Disorders. 2002. Stockholm, Sweden.
10
Hadland, BK et al. Gamma -secretase inhibitors repress thymocyte development. Proc Natl Acad Sci. 2001 Jun 19;98(13):7487-9.
PubMed |
